The COMPARE head-to-head, randomized controlled trial of SEL-212 (pegadricase plus rapamycin-containing nanoparticle, ImmTOR™) versus pegloticase for refractory gout

• Published in: Rheumatology (Oxford, England) Vol. 63; no. 4; pp. 1058 - 1067
• Main Authors: Baraf, Herbert S B, Khanna, Puja P, Kivitz, Alan J, Strand, Vibeke, Choi, Hyon K, Terkeltaub, Robert, Dalbeth, Nicola, DeHaan, Wesley, Azeem, Rehan, Traber, Peter G, Keenan, Robert T
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 02.04.2024
• Subjects: Adult; Clinical Science; Gout; Gout Suppressants - adverse effects; Gout Suppressants - therapeutic use; Humans; Polyethylene Glycols - adverse effects; Polyethylene Glycols - therapeutic use; Stomatitis - chemically induced; Stomatitis - drug therapy; Symptom Flare Up; Treatment Outcome; Urate Oxidase - adverse effects; Urate Oxidase - therapeutic use; Uric Acid; Uricosuric Agents - adverse effects; Uricosuric Agents - therapeutic use; pegloticase; SEL-212; gout; nanotechnology; uricase; pegadricase; serum urate; rapamycin
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kead333

Serum urate (SU) lowering with PEGylated uricases in gout can reduce flares and tophi. However, treatment-emergent anti-drug antibodies adversely affect safety and efficacy and the currently approved PEGylated uricase pegloticase requires twice-monthly infusions. Investigational SEL-212 therapy aims to promote uricase-specific tolerance via monthly sequential infusions of a proprietary rapamycin-containing nanoparticle (ImmTOR) and pegadricase. COMPARE was a randomized, phase 2, open-label trial of SEL-212 vs pegloticase in adults with refractory gout. SEL-212 [ImmTOR (0.15 mg/kg) and pegadricase (0.2 mg/kg)] was infused monthly or pegloticase (8 mg) twice monthly for 6 months. The primary endpoint was the proportion of participants with SU <6 mg/dl for ≥80% of the time during 3 and 6 months. Secondary outcomes were mean SU, gout flares, number of tender and/or swollen joints and safety. During months 3 and 6 combined, numerically more participants achieved and maintained a SU <6 mg/dl for ≥80% of the time with SEL-212 vs pegloticase (53.0% vs 46.0%, P = 0.181). The percentage reductions in SU levels were statistically greater during months 3 and 6 with SEL-212 vs pegloticase (-73.79% and -47.96%, P = 0.0161). Reductions in gout flare incidence and number of tender and/or swollen joints were comparable between treatments. There were numerical differences between the most common treatment-related adverse events of interest with SEL-212 and pegloticase: gout flares (60.2% vs 50.6%), infections (25.3% vs 18.4%) and infusion-related reactions (15.7% vs 11.5%), respectively. Stomatitis (and related terms) was experienced by eight participants (9.6%) with SEL-212 and none with pegloticase. Stomatitis, a known event for rapamycin, was associated with ImmTOR only. SEL-212 efficacy and tolerability were comparable to pegloticase in refractory gout. This was associated with a substantial reduction in treatment burden with SEL-212 due to decreased infusion frequency vs pegloticase. NCT03905512.